The overall purpose of this application is to refine existing techniques and to develop new biochemical models, methods, and experimental techniques for autoradiographic and magnetic resonance imaging of cerebral blood flow and metabolism and their interrelationships. The development of a very high performance, low cost imaging system for quantitative analysis and three dimensional processing and display of autoradiographic images will be completed. The system uses newly-developed memory-intensive, lookup table-based algorithms to achieve very rapid effective processing speeds on personal computers. The system will be used for three dimensional quantitative analysis of autoradiograms of cerebral blood flow and metabolism tracers in animals. Double and triple label autoradiographic techniques will be developed for concurrent and sequential tracer studies. Using these techniques, the kinetics of various metabolic tracers will be compared. Results of these studies will be used to evaluate existing kinetic models, and to assess the significance and limitations of their basic assumptions. From this base, new methods for estimatiOn of cerebral glycolysis and oxidation will be developed. The metabolic studies will then be combined with studies of blood flow under normal and abnormal conditions. Based on autoradiographic studies, corresponding magnetic resonance (MR) imaging and spectroscopic studies will be performed In humans to evaluate the relationships between cerebral blood flow (deoxyhemoglobin-shift imaging) and cerebral metabolism (lactate spectroscopy). The basic understanding of cerebral metabolism and blood flow provided by these studies will promote greater understanding of the function of the brain in normal and pathological conditions in animal models (autoradiography) and in humans (MR).